Abstract
Regulated cell death (RCD) contributes to reshaping the tumor immune microenvironment and participating in the progression of non-small cell lung cancer (NSCLC); however, related mechanisms have not been fully disclosed. Here, we identified 5 subclusters of NSCLC based on consensus clustering of 3429 RCD-associated genes in the TCGA database and depicted the genomic features and immune landscape of these clusters. Importantly, the clusters provided insights into recognizing tumor microenvironment (TME) and tumor responses to immunotherapy and chemotherapy. Further, we established and validated an RCD-Risk model based on RCD-associated genes, which strongly predicted the prognosis, TME, and immunotherapy outcomes in NSCLC patients. Notably, tissue microarray staining confirmed that the expression of LDLRAD3, a core gene in RCD-Risk model, correlated with poor survival. In conclusion, we developed a novel RCD classification system and RCD-Risk model of NSCLC, serving as a robust and promising predictor for prognosis and immunotherapy benefit of individual NSCLC patients.